Dispenser with doses′ counter

ABSTRACT

There is provided a dispenser suitable for dispensing medicament, particularly medicament for use in the treatment of respiratory disorders. The dispenser comprises a housing ( 1 ) having a support ( 5 ); a container ( 2 ), locatable within said housing ( 1 ), having an outlet member, wherein said container ( 2 ) is movable relative to the housing ( 1 ) to enable dispensing therefrom and said outlet member is connectable with said support ( 5 ) to prevent relative movement there-between; and a dose indicator ( 13, 43 ), locatable within said housing ( 1 ). The container ( 2 ) and dose indicator ( 13, 43 ) are reversably removable from the housing ( 1 ) as a single unit.

This application is filed pursuant to 35 U.S.C. §371 as a United StatesNational Phase Application of International Application No.PCT/EP98/03377 filed Jun. 8, 1998, which claims priority fromGB9711889.7 filed Jun. 8, 1997 and GB9721875.4 on Oct. 16, 1997

The present invention relates to a dispenser having an actuationindicator for indicating the number of actuations thereof. Inparticular, the invention relates to metered dose inhalers by means ofwhich medicaments contained in an aerosol container may be administeredto a patient.

It is well known to treat patients with medicaments contained in anaerosol, for example, in bronchoditator therapy. It is also known to usefor such therapy, medicaments which are contained in an aerosol and areadministered to a patient by means of an inhalation device comprising atubular housing or sleeve in which the aerosol container is located andan outlet tube leading out of the tubular housing. The aerosolcontainers used in such inhalation devices are designed to deliver apredetermined dose of medicament upon each actuation by means of anoutlet valve member at one end which can be opened either by depressingthe valve member while the container is held stationary or by depressingthe container while the valve member is held stationary. In the use ofsuch devices, the aerosol container is placed in the tubular housingwith the outlet valve member of the container communicating via asupport with the outlet tube, for example a nozzle or mouthpiece. Whenused for dispensing medicaments, for example in bronchodilation therapy,the housing is then held by the patient in a more or less uprightcondition and the mouthpiece or nozzle of the inhalation device isplaced in the mouth or nose of the patient. The aerosol container ispressed towards the support to dispense a dose of medicament from thecontainer which is then inhaled by the patient.

A disadvantage arising from use of such known devices is that thepatient cannot determine the amount of medicament in the container atany given time. In an extreme case this could mean that the patient,possibly suffering from severe bronchospasm and needing a dose ofmedicament, will find that the container will not dispense a dosebecause its contents have already been exhausted.

U.S. Pat. No. 4,817,822 describes an aerosol dispenser of the typedescribed above having a dose indicating device which, in a firstembodiment is removably attached to the end of the protruding portion ofthe aerosol container. The operating mechanism of the dose counter islocated within a housing which extends from the end of the aerosolcontainer along the external surface of the tubular housing. It isimportant with inhalation devices containing medicament that thecontents of the aerosol container are clearly marked to ensure that thepatient knows exactly what medication is contained. One disadvantageassociated with this positioning of the dose indicating device is thatthe device obscures at least a part of the aerosol container and housingwhich creates labelling difficulties.

A further disadvantage of the device described is that if the doseindicating device is removably attached to the aerosol container, it ispossible that the dose indicating device may become separated from itsaerosol container with the result that the aerosol dispenser could beused without the dose indicating device, or the actuating mechanism ofthe indicating device could be tampered with leading to a false readingwhen the indicating device is re-attached to the dispenser. Withpatients having several different inhalers, it could even result in theindicating device being re-attached to the wrong dispenser.

In a second embodiment described in U.S. Pat. No. 4,817,822 theoperating mechanism of the dose indicating device is located within acompartment in the housing and is actuated by means of an actuatormember attached to the aerosol container. In this embodiment, once theaerosol container is fitted into the housing it cannot be removed. Thismakes cleaning of the housing very difficult. Even if the container wereremovable, the operating mechanism of the dose indicating device wouldbe vulnerable to damage when washing with water, soap, disinfectant orantiseptic solutions. This is important because sprays of many aerosolformulations leave residues which can entrap dust and dirt particles.Some provide a media for the growth of undesired micro-organisms. If thegrowth of these micro-organisms is unchecked, they can serve as a sourceof infection for the patient and will often introduce pathogens into thepatient's respiratory tract.

WO96/16686 describes an aerosol dispenser wherein the operatingmechanism of the dose indicating device is electronic and wherein theactuating member comprises a microswitch set into the wall of thehousing. The electronic counting mechanism and microswitch are containedwithin a hermetically sealed enclosure. However, electronic assembliesof this type are relatively expensive compared to equivalent mechanicalmechanisms, typically costing five or six times as much to producedepending on quantities manufactured. Such expense must ultimately beborne by the customer and may be prohibitive.

U.S. Pat. No. 5,482,030 describes an aerosol dispenser having amechanical dose indicator device located in and connected to the housingin the vicinity of the outlet tube of the aerosol container when fitted.Its mechanical construction makes it difficult to seal against moistureingress and so this dispenser again is difficult to wash withoutdamaging the operating mechanism of the dose indicating device.

Many different pharmaceutical products are sold in the form of aerosolcontainers as discussed above, requiring different sized containerbodies and/or valves according to the required specifications. It istherefore normal for there to be dimensional variations betweendifferent aerosol containers. Even between the same products there canbe dimensional variations due to manufacturing tolerances. One problemwhich is common to all of the dose indicating devices discussed above isthat the indicator mechanism, which is actuated by means of a switchwhich detects relative movement between the container body and housing,lacks any means of compensating for dimensional variations betweendifferent aerosol containers. Hence, the indicators described must bedimensioned according to the product with which they are to be used, andso will not be interchangeable with other products. Furthermore, inorder for the dose indicators to work properly, the dimensions of theindicator, aerosol container and housing must be accurate.

It is an object to provide a dispenser having an actuation indicatorwhich overcomes at least some of the above described disadvantages. Itis a further object to provide such a dispenser which from the point ofview of the patient closely resembles currently marketed dispensers inboth external appearance and operation.

According to one aspect of the present invention there is provided adispenser for dispensing medicament comprising a housing having asupport; a container, locatable within said housing, having an outletmember, wherein said container is movable relative to the housing toenable dispensing therefrom and said outlet member is connectable withsaid support to prevent relative movement therebetween; and an actuationindicator, locatable within said housing, wherein the container and doseindicator are reversably removable from the housing as a single unit.

Suitably, the actuation indicator is engagable with the container in thevicinity of the outlet member. More preferably, the actuation indicatoris engagable with the outlet member.

Suitably, the actuation indicator is provided with a grip member whichis engagable with a neck portion of the container. Preferably, the neckportion is adjacent to or on the outlet member.

Suitably, the container is an aerosol container.

Suitably, the housing is provided with an outlet, more preferably in theform of a mouthpiece. Preferably, the dispenser comprises a passagethrough which dispensed doses may pass from the container to the outlet.

Suitably, the container provides measured doses.

Suitably, the actuation indicator indicates the number of dosesdispensed from or remaining in the container.

Suitably, the actuation indicator comprises an indexing mechanismactuated by a predetermined movement of the aerosol container relativeto the housing.

Preferably, the indexing mechanism comprises a lost motion coupling toallow and compensate for excess movement (‘overtravel’) of the aerosolcontainer relative to the housing.

By use of a lost motion coupling it is possible to create an actuationindicator of one size which can accomodate valves and actuators madewithin a wide range of manufacturing tolerances and can even fit a rangeof dispensers made to different dimensions.

Suitably, the indexing mechanism indexes the actuation indicator bymeans of a predetermined rotary movement of a first member driven bymovement relative to a second member during actuation of the aerosoldispenser.

Suitably, the second member remains stationary relative to the housingduring actuation of the aerosol dispenser.

Suitably, the first member comprises a pinion carried by a shaft throughthe lost motion coupling and the second member comprises a rack.Alternatively, the first member comprises a yoke and the second membercomprises a post engaged by the yoke through the lost motion coupling.

Preferably, the lost motion coupling comprises a friction drivemechanism.

Suitably, the dispenser is a breath operated inhaler which is actuablein response to the inward breath of a user.

According to a particularly preferred aspect of the present inventionthere is provided an aerosol dispenser comprising a housing in which acontainer is removably located, an outlet leading from the housing and asupport in the housing arranged to receive an outlet member of thecontainer and having a passage through which the contents of thecontainer may pass to the outlet, the outlet member being heldstationary in the housing support and the body of the container beingmoveable relative to the outlet and housing to dispense its contents inmeasured doses, and a dose indicating device having a dose indicator forindicating the number of doses dispensed from or remaining in thecontainer, characterised in that the dose indicating device is tightlyconnected to the container in the vicinity of the outlet member, suchthat the container and dose indicating device may be removed from thehousing as a single unit.

According to a further aspect of the present invention there is providedan actuation indicating device for use with a dispenser comprising ahousing and a container, locatable within said housing, having an outletmember, the actuation indicating device comprising attachment means toenable attachment to the container.

Suitably, the attachment means comprises a grip member which firmlyengages a neck portion formed around the container. More preferably, theneck portion is located at the connection between the container andoutlet member.

According to a particularly preferred aspect of the present inventionthe actuation indicating device has an actuation indicator forindicating the number of doses dispensed from or remaining in thecontainer, wherein the actuation indicating device comprises attachmentmeans to enable tight connection to the container in the vicinity of theoutlet member.

By fixing the actuation indicating device to the container in thevicinity of the outlet member may be possible to make use of thephysical dimensions of the crimped ferrule of standard containers toprovide a tight snap fit between the dose indicating device and aerosolcontainer for easy assembly yet which once assembled cannot be easilyseparated. This ensures that the actuation indicator presents accurateinformation concerning the container with which it is assembled.

In a preferred aspect, the dispenser is a metered dose inhalercomprising a housing in which the container is removably located, anoutlet leading from the housing, a support in the housing arranged toreceive the outlet member of the container and having a passage throughwhich the contents of the container may pass to the outlet, the outletmember being held stationary in the housing support and the body of thecontainer being moveable relative to the outlet and housing to dispenseits contents in measured doses, and a window through which the doseindicator may be viewed.

The location of the dose indicator in the vicinity of the outlet memberof the container in a metered dose inhaler provides the advantage thatvisually and operationally the device may appear very similar to currentmarketed metered dose inhalers without dose indicating devices such thatwhen switched to the metered dose inhaler according to the invention,patients perceive little change over their conventional dispensers, socreating minimal impact upon patients and their use of the device.

A dispenser according to the invention will now be described withreference to the accompanying drawings in which:

FIG. 1 is a section through a standard inhalation device comprising anaerosol dispenser;

FIG. 2 is a section through the dose indicating device as fitted to anaerosol dispenser in an inhalation device;

FIG. 3 is a perspective view of a counting mechanism used in the doseindicating device of FIG. 2;

FIG. 4 shows the sequence of operation of the counter mechanism of FIG.3;

FIG. 5 shows a lateral and a longitudinal section through a secondembodiment of the dose indicating device as fitted into the housing ofan inhalation device;

FIG. 6 shows an exploded view of a dose indicating device according to athird embodiment of the invention;

FIG. 7 shows another exploded view of the dose indicating device of FIG.6 together with an aerosol container and housing;

FIG. 8 shows a schematic section through an inhalation device comprisingthe dose indicating device of FIG. 6 in a rest position; and

FIG. 9 shows a schematic section through the inhalation device of FIG. 8in an actuated position.

The standard metered dose inhaler shown in FIG. 1 comprises a tubularhousing 1 in which an aerosol container 2 can be located. The housing isopen at one end (which, will hereinafter be considered to be the top ofthe device for convenience of description) and is closed at the other.An outlet 3 leads laterally from the closed end of the housing 1. In theembodiment illustrated, the outlet 3 is in the form of a mouthpieceintended for insertion into the mouth of the patient but it may, ifdesired, be designed as a nozzle for insertion into the patient'snostril.

The aerosol container 2 has an outlet valve stem 4 at one end. Thisvalve member can be depressed to release a measured dose from theaerosol container or, alternatively, the valve stem 4 can be fixed andthe main body of the container can be moved relative to the valve memberto release the dose.

As shown clearly in FIG. 1, the aerosol container 2 is located in thehousing 1 so that one end protrudes from its open top. Spacer ribs (notshown) may be provided inside the housing to hold the external surfaceof the container 2 spaced from the internal surface of the housing 1. Asupport 5 is provided at the lower end of the housing 1 and has apassage 6 in which the valve stem 4 of the aerosol container 2 can belocated and supported. A second passage 7 is provided in the support 5and is directed towards the interior of the outlet 3. Thus, when theparts are in the positions shown in FIG. 1, the protruding portion ofthe aerosol container 2 can be depressed to move the container relativeto the valve stem 4 to open the valve and a dose of medicament containedin the aerosol will be discharged through the passage 7 and into theoutlet 3 from which it can be inhaled by a patient. One dose will bereleased from the aerosol container each time it is fully depressed.

FIG. 2 shows the lower part of a device similar to that of FIG. 1 butincorporating a dose indicating device according to the invention. Thedose indicating device comprises a body 8 firmly attached to the aerosolcontainer by means of tubular portion 9 formed with lip 10. Tubularportion 9 tightly engages the periphery of valve ferrule 11 while a gripin the form of lip 10 engages around neck 12 of valve ferrule 11 whichis formed during assembly when valve ferrule 11 is crimped onto aerosolcontainer 2. Thus the tubular portion 9 and lip 10 form a tightconnection to the aerosol container which once assembled by pushing thetubular portion 9 over the valve ferrule 11 cannot easily be dissembled.

Below tubular portion 9, body 8 forms a cradle 22 for mounting countermechanism 13 and drive pinion 14. Drive pinion 14 is friction mounted oncounter mechanism drive shaft 15. Drive pinion 14 is formed with anumber of teeth or pegs 21 which can engage with a number of recesses orgrooves formed on post 17 in the form of a rack moulded inside housing 1and extending from the base of the housing 1 parallel to valve stem 4.

Whilst in the embodiment shown in FIG. 2 the post 17 forms a mouldedpart of the housing other variations can be envisaged in which the post17 forms a part of the dose indicating device itself. For example, FIG.2a shows a simplified representation of a dose indicating device inwhich the head of post 17 is receivable within a recess provided in thebody 8 of the device. Teeth formed on the post 17 engage correspondingteeth on drive pinion 14. Spring 28 acts such as to urge the post fromthe recess. The protruding lip 24 of the post 17, however, abuts stop26, thereby retaining at least a portion of the post 17 within therecess.

As shown in FIGS. 3 and 4, drive shaft 15 is connected to driver yoke 16of counter mechanism 13. Driver yoke 16 has two switching latches 18 aand 18 b spaced either side of star wheel 19 such that driver yoke 16may tilt about the axis of drive shaft 15 between a first position shownin FIG. 4b in which switching latch 18 a engages one side of star wheel19, and a second position shown in FIG. 4d in which switching latch 18 bengages the other side of star wheel 19. Star wheel 19 is connectedthrough a mechanism, similar to that described with reference toreference numerals 2 to 8 in FIGS. 1 to 3 of European Patent No.0280104, to three digit wheels 33, which have numbers printed on theircircumferential faces as described below. When located in the housing 1,counter mechanism 13 is small enough to be located to the sides of andbehind support 5 so as not to interfere with the aerosol flume as itemerges from passage 7.

The aerosol container 2 may be supplied to the patient with the doseindicating device ready assembled thereto. Alternatively, the housing 1may be supplied to the patient with the dose indicating device locatedin the position shown in FIG. 2 and the aerosol container 2 suppliedseparately. In this case, the patient is instructed to insert theaerosol container 2 into the housing 1 with the valve stem first. Uponfirst insertion of the container into the housing, the tubular portion 9and lip 10 of the dose indicating device ride over the periphery ofvalve ferrule 11 of the aerosol container 2 until lip 10 snaps aroundneck 12. Thereafter, the dose indicating device is attached to theaerosol container 2.

Other means of attachment of the dose indicator to the container areenvisaged including adhesive attachment; use of welded shrink sleeves;heat forming; crimping; ultra-sonic welding; and by the presence of ano-ring elastomer on the container which is fixedly piercable by barbs onthe attachment member of the dose indicator. In one aspect, permanentmeans of attachment are preferred.

To actuate the device, the protruding portion of the aerosol containeris depressed as described above with reference to FIG. 1. As the aerosolcontainer carrying the dose indicating mechanism moves within housing 1,drive pinion 14 starts to turn, through its engagement with post 17,causing rotation of drive shaft 15 and driver yoke 16. As driver yoke 16tilts with rotation of drive shaft 15 switching latch 18 a moves intoengagement with star wheel 19 (FIG. 4a) causing an incrementalanti-clockwise rotation of a half tooth pitch of the star wheel untilthe switching latch 18 a can move no further in this direction, theswitching latch being positioned between two adjacent teeth of the starwheel (FIG. 4b). At this point, drive shaft 15 cannot rotate any furtherand any further movement of the aerosol container into housing 1 resultsin drive pinion 14 continuing to rotate through its engagement with post17 by virtue of the friction coupling between pinion 14 and drive shaft15.

When the valve stem 4 has reached its fully depressed position and ametered dose of medicament has been discharged from the aerosolcontainer, the aerosol container is allowed to return to its originalposition. As the aerosol container and dose indicating mechanism returnto their original position, drive pinion 14 starts to rotate in theopposite direction together with drive shaft 15 and driver yoke 16.Thus, driver yoke 16 tilts such that switching latch 18 a moves out ofengagement with star wheel 19 while switching latch 18 b moves intoengagement therewith (FIG. 4c), causing further incrementalanti-clockwise rotation of a half tooth pitch of the star wheel untilswitching latch 18 b can move no further in this direction (FIG. 4d).Again, drive shaft 15 cannot rotate any further at this point and anyfurther movement of the aerosol container out of housing 1 results indrive pinion 14 continuing to rotate through its engagement with post 17by virtue of the friction coupling between pinion 14 and drive shaft 15.In this way it can be seen that the friction coupling acts as a lostmotion coupling which allows the dose indicating device to be used withaerosol containers having valves with different lengths of travel ofvalve stem during actuation.

Each time the aerosol dispenser is actuated the star wheel is made torotate through two incremental anti-clockwise movements as describedabove. These movements are translated through the counter mechanism intoappropriate movements of the digit wheels 33, one number on each of theprinted circumferential faces of the digit wheels being clearly visiblethrough the window 20 at the back of the housing 1 (as shown in FIG. 2),to indicate that a further dose of medicament has been dispensed. Byhaving three digit wheels 33 it is possible for the dose counter to beused to count hundreds of doses. Clearly if fewer than one hundred dosesare to be contained within the dispenser, the dose counter couldcomprise fewer digit wheels. Alternatively, if a thousand or more dosesare to be contained, then one or more additional digit wheels could beadded as appropriate.

To remove the aerosol container 2 from the housing for cleaning, theaerosol container 2 may be withdrawn from the housing 1 in the usualmanner. As the container is withdrawn, the friction coupling betweendrive pinion 14 and drive shaft 15 allows such further movement as isrequired for the drive pinion to come out of engagement with the post 17without causing any further indexing of the counter mechanism. Onceremoved, the housing 1 may be cleaned as described without fear ofinterfering with or damaging the dose indicating device, which remainsfirmly connected to the aerosol container 2.

When the housing 1 is clean, the aerosol container 2 with doseindicating device may be re-inserted into the housing 1. Duringinsertion, drive pinion 14 will engage post 17 and start to rotate untilthe aerosol container reaches its normal rest position with the valvestem 4 located in support 5. As the drive pinion 14 rotates, thefriction coupling will act as a lost motion mechanism as describedabove, allowing for any travel of the aerosol container as between firstengagement of drive pinion 14 and post 17, and location of valve stem 14in support 5. In this way, the friction coupling automaticallyaccommodates and compensates for different lengths of valve stemsprotruding from the ferrule.

FIG. 5 shows an alternative lost motion coupling mechanism which may beused in an aerosol dispenser according to the invention. In thisembodiment, instead of a pinion, driver yoke 16 is formed with tworesilient arms 30 between which post 17 is grippingly engaged (FIG. 5a).Post 17 is formed with ribs on its surface (not shown) which provide arough surface finish to create the level of friction required betweenarms 30 and post 17 such that arms 30 will grip post 17 until the loadapplied overcomes the friction.

Upon actuation of the device, as the aerosol container and doseindicating mechanism move, the friction engagement between arms 30 andpost 17 cause driver yoke 16 to tilt about the axis of shaft 15 (notshown in FIG. 5), so moving switching latch 18 a into engagement withstar wheel 19 as discussed in relation to the first embodiment. Asswitching latch 18 a reaches its limit of travel, driver yoke 16 canmove no further, and any further movement of the aerosol container intohousing 1 results in arms 30 slipping down post 17 by virtue of thefriction coupling. Upon return to its original position, driver yoke 16tilts in the other direction until switching latch 18 b moves intoengagement with star wheel 19 and can move no further. Any furthermovement of the aerosol container out of housing 1 results in arms 30slipping up post 17.

FIGS. 6 to 9 show an inhalation device fitted with an electro-mechanicaldose indicating device according to the invention. As with themechanical embodiments discussed above, the dose indicating devicecomprises a body 40 firmly attached to the aerosol container by means oftubular portion 41 formed with grips (not shown). Tubular portion 41tightly engages the periphery of valve ferrule 11 while a grip in theform of a lip engages around neck 12 of valve ferrule 11. Thus thetubular portion 41 and lip form a tight connection to the aerosolcontainer which once assembled by pushing the tubular portion 41 overthe valve ferrule 11 cannot easily be disassembled.

Below tubular portion 41, body 40 forms a cradle for mounting countermechanism 43, and defines a chamber for accommodating switch slide 44.Switch slide 44 is a cylindrical washer made of silicone rubber andhaving a bore of such a diameter that, with the can and dose indicatingdevice mounted within the actuator housing, it provides a friction fiton pin 45, which is moulded in the housing and protrudes through a holein body 40. The friction fit of switch slide 44 on pin 45 ensures theswitch slide will not move along the pin unless pushed. Two contactmembers 46, 47, both of which comprise a switch contact and a circuitboard contact, and one of which further comprises a battery contact, aremounted such that the battery and circuit board contacts are in constantcontact with a first terminal of the battery 48 and printed circuitboard (PCB) 49 respectively. The switch contacts do not contact eachother but are positioned either side of pin 45, and define the upperlimit of movement of the switch slide 44 within its chamber. Thus, whenswitch slide 44 is in its upper position as shown in FIG. 9, it makescontact with both switch contacts, so closing the circuit between themdue to the electrical conductivity of the silicone rubber of the switchslide. Although in the embodiment described the switch slide is made ofsilicone rubber, it will be appreciated that it could alternatively bemade of a non-conductive rubber having an insert at its upper face madeof metal or some other conductive material.

In addition to its connections with contact members 46, 47, PCB 49 alsohas connections to the other terminal of the battery and to a threedigit liquid crystal display (LCD) 50 in a conventional manner. The PCBcomprises an application specific integrated circuit (ASIC), whichprovides the logic by which the dose indicator can be checked,programmed and made operational, as discussed in more detail below. tokeep a record of how many times the switch contact circuit is closed anddrives the LCD to display the number of doses remaining in the aerosolcontainer. The ASIC is thus designed and programmed accordingly in aknown manner.

Instead of a digital display, the LCD could alternatively be formattedto display an analogue indication. When the aerosol container is mountedin the actuator housing, LCD 50 is visible through window 20. In theembodiment depicted in FIG. 7, the LCD and window are located at theback of the housing, but they could equally be located at the front orsome other part of the housing.

The Counter mechanism 43 is small enough to be located to the sides ofand behind the stem block (support 5) moulded in housing so as not tointerfere with the aerosol flume as it emerges.

To actuate the device, the protruding portion of the aerosol containerwhen fitted into the actuator housing is depressed as described above.As the aerosol container carrying the dose indicating mechanism moveswithin the housing from its rest position (shown in FIG. 8), the chamberaccommodating switch slide 44 moves down until the upper face of switchslide 44, which is mounted on pin 45, meets switch contacts 46, 47 andthe switch circuit is closed. This causes the ASIC to decrement thenumber displayed by the LCD 50. As the aerosol container continues tomove, a metered dose of medicament is discharged from the valve, whileswitch slide 44 is pushed down along pin 45 by virtue of the frictionfit of the switch slide on the pin until the valve stem reaches itslimit of travel and the aerosol container moves no further (FIG. 9). Inthis way, it can be seen that the friction fit of the switch slide 44 onpin 45 allows for over-travel of the valve stem after the switch circuithas been closed, so acting as a lost motion coupling. The aerosolcontainer is then allowed to return to its original position within thehousing, and as it returns, the chamber accommodating switch slide 44moves up breaking the switch circuit as switch contacts 46, 47 move awayfrom switch slide 44. Body 40 then meets the lower face of switch slide44 and draws the switch slide up along pin 45 until the valve stemreturns to its rest position (FIG. 8).

Because the dose indicating device is designed to be suitable for use inconnection with different sized aerosol containers containing differentnumbers of doses to be delivered, the ASIC is designed to be factory setin accordance with the size of aerosol container with which the doseindicating device is assembled. After assembly of the dose indicatingdevice and first connection of the battery, the ASIC enters a self-testmode. After this, the programming mode may be entered by activating theswitch, allowing it to be programmed to count down from the appropriatenumber of doses (e.g. 200, 120, 80 or 60). This may be doneautomatically on a packing line. After programming has taken place, theASIC enters the counting mode, where the LCD decrements upon closing ofthe switch contact circuit. When the count of zero is reached, the ASICis designed to prevent the count from decrementing any further in aknown manner. In order to prevent spurious readings due to the effectsof switch ‘bounce’, the ASIC may be designed to decrement only after theswitch circuit has been closed for a predetermined length of time in aknown manner. In the event of the aerosol container getting jammed inthe actuated position after operation, or the switch circuit jammingclosed due to mechanical damage or contamination, the ASIC may bedesigned to blank the LCD to alert the user that there is a problem.

As with the other embodiments of the invention described above, theaerosol container may be withdrawn from the actuator housing in theusual manner. As the container is withdrawn, body 40 draws the switchslide up along pin 45 until it clears the pin altogether. Once removed,the housing may be cleaned without interfering with or damaging the doseindicating device, which remains firmly connected to the aerosolcontainer.

During re-insertion of the aerosol container, which can only occur whenthe body of the dose indicating device is correctly orientated withrespect to the housing by virtue of their respective shapes, switchslide 44 engages and is pushed up by pin 45 until the upper face meetsthe switch contacts. Further insertion of the aerosol container resultsin switch slide 44 being pushed down along pin 45 until the valve stemis seated back within support 5.

It will be appreciated that by programming of the ASIC, one design ofdose indicating device could be used in conjunction with a range ofaerosol containers of various capacities. By virtue of the switchmechanism, the same design of dose indicating device can also be used inconjunction with a range of different valves having different lengths ofvalve stem and different stem travel specifications.

Whilst the present invention has been described in detail in respect ofa metered dose inhaler actuatable manually by the patient it will beappreciated that other actuation mechanisms can be substituted. Inparticular, the use of a breath operated inhaler in which the actuationis assisted, and is responsive to, preferably triggered by, the inwardbreath of the patient, is also envisaged.

The dispenser of the invention is suitable for dispensing medicament,particularly for the treatment of respiratory disorders. Appropriatemedicaments may thus be selected from, for example, analgesics, e.g.,codeine, dihydromorphine, ergotamine, fentanyl or morphine; anginalpreparations, e.g., diltiazem; antiallergics, e.g., cromoglycate,ketotifen or nedocromil; antiinfectives e.g., cephalosporins,penicillins, streptomycin, sulphonamides, tetracyclines and pentamidine;antihistamines, e.g., methapyrilene; anti-inflammatories, e.g.,beclomethasone dipropionate, fluticasone propionate, flunisolide,budesonide, rofleponide, mometasone furoate or triamcinolone acetonide;antitussives, e.g., noscapine; bronchodilators, e.g., albuterol,salmeterol, ephedrine, adrenaline, fenoterol, formoterol, isoprenaline,metaproterenol, phenylephrine, phenylpropanolamine, pirbuterol,reproterol, rimiterol, terbutaline, isoetharine, tulobuterol, or(−)-4-amino-3,5-dichloro-α-[[[6-[2-(2-pyridinyl)ethoxy]hexyl]methyl]benzenemethanol; diuretics, e.g., amiloride;anticholinergics, e.g., ipratropium, tiotropium, atropine or oxitropium;hormones, e.g., cortisone, hydrocortisone or prednisolone; xanthines,e.g., aminophylline, choline theophyllinate, lysine theophyllinate ortheophylline; therapeutic proteins and peptides, e.g., insulin orglucagon. It will be clear to a person skilled in the art that, whereappropriate, the medicaments may be used in the form of salts, (e.g., asalkali metal or amine salts or as acid addition salts) or as esters(e.g., lower alkyl esters) or as solvates (e.g., hydrates) to optimisethe activity and/or stability of the medicament.

Preferred medicaments are selected from albuterol, salmeterol,fluticasone propionate and beclometasone dippropionate and salts orsovates thereof, e.g., the sulphate of albuterol and the xinafoate ofsalmeterol.

Medicaments can also be delivered in combinations. Preferredformulations containing combinations of active ingredients containsalbutamol (e.g., as the free base or the sulphate salt) or salmeterol(e.g., as the xinafoate salt) in combination with an antiinflammatorysteroid such as a beclomethasone ester (e.g., the dipropionate) or afluticasone ester (e.g., the propionate).

It will be understood that the present disclosure is for the purpose ofillustration only and the invention extends to modifications, variationsand improvements thereto.

The application of which this description and claims form part may beused as a basis for priority in respect of any subsequent application.The claims of such subsequent application may be directed to any featureor combination of features described therein. They may take the form ofproduct, method or use claims and may include, by way of example andwithout limitation, one or more of the following claims:

What is claimed is:
 1. A dispenser for dispensing medicament comprisinga housing having a support; a container, locatable within said housing,having an outlet member, wherein said container is movable relative toan housing to enable dispensing therefrom and said outlet member isconnectable with said support to prevent relative movement therebetween;and an actuation indicator, locatable within said housing, wherein thecontainer and actuation indicator are reversably removable from thehousing as a single unit.
 2. A dispenser according to claim 1 whereinthe actuation indicator is engagable with the container in the vicinityof said outlet member.
 3. A dispenser according to claim 2 wherein theactuation indicator is engagable with the outlet member.
 4. A dispenseraccording to claim 1, wherein the actuation indicator is provided with agrip member which is engagable with a neck portion of the container. 5.A drug product according to claim 4, wherein the neck portion isadjacent to or on the outlet member.
 6. A drug product according toclaim 1 wherein the container is an aerosol container.
 7. A dispenseraccording to claim 1 wherein the housing is provided with an outlet,preferably in the form of a mouthpiece.
 8. A dispenser according toclaim 7 comprising a passage through which dispensed doses may pass fromthe container to said outlet.
 9. A dispenser according to claim 1wherein said container provides measured doses.
 10. A drug productaccording to claim 1 wherein said actuation indicator indicates thenumber of doses dispensed from or remaining in the container.
 11. Adispenser according to claim 1, wherein the actuation indicatorcomprises an indexing mechanism actuated by a predetermined movement ofthe container relative to the housing.
 12. A dispenser according toclaim 11, wherein the indexing mechanism comprises a lost motioncoupling to allow and compensate for excess movement of the containerrelative to the housing.
 13. A dispenser according to claim 12, whereinthe indexing mechanism indexes the actuation indicator by means of apredetermined rotary movement of a first member driven by movementrelative to a second member during actuation of the dispenser.
 14. Adispenser according to claim 12 13, wherein the first member comprises apinion carried by a shaft through the lost motion coupling and thesecond member comprises a rack.
 15. A drug product according to claim 1,actuable in response to the inward breath of a user.
 16. The drugproduct of claim 1 wherein the container is movable relative to thehousing to enable dispensing therefrom, and the outlet member isconnectable with the support to prevent relative movement therebetween.17. A drug product comprising: an aerosol canister including a cancontaining a drug formulation comprising a propellant and a medicament;a valve having a valve stem: an actuator removably engaging the aerosolcanister; and, an actuation indicator fixedly engaging the aerosolcanister. wherein the fixedly engaged container and actuation indicatorare reversibly removable as a single unit.
 18. The drug product of claim17, wherein the actuation indicator includes a drive shaft frictionallycoupled to a pinion, a post engaging the pinion, a yoke engaging thedrive shaft, and, first and second switching latches engaging a starwheel, wherein the drive shaft, yoke, and pinion, wherein each rotate ina plane longitudinal to movement of the aerosol canister.
 19. The drugproduct of claim 17, wherein the actuation indicator is fixed to theaerosol canister by a barbed tang fixedly engaging a ferrule fixed tothe can.
 20. The drug product of claim 17, wherein the actuationindicator is fixed to the aerosol canister by an adhesive, a weldedshrink sleeve, a heat form, a crimp, an ultrasonic weld, an o-ringelastomer.
 21. The drug product of claim 17, wherein the actuationindicator is permanently attached to the aerosol canister.
 22. The drugproduct of claim 17, wherein the medicament is selected from the groupconsisting of beclomethasone, fluticasone, flunisolide, budesonide,rofleponide, mometasone, triamcinolone, noscapine, albuterol,salmeterol, ephedrine, adrenaline, fenoterol, formoterol, isoprenaline,metaproterenol, terbutaline, tiotropium, ipratropium, phenylephrine,phenylpropanolamine, pirbuterol, reproterol, rimiterol, isoetharine,tulobuterol,(−)-4-amino-3,5-dichloro-α-{{{6-{2-(2-pyridinyl)ethoxy}hexyl}methyl}benzenemethanol,esters, solvates and salts thereof, and combinations thereof.
 23. Thedrug product of claim 17, wherein the medicament is albuterol sulphate.24. The drug product of claim 17, wherein the medicament is salmeterolxinafoate.
 25. The drug product of claim 17, wherein the medicament isfluticasone propionate.
 26. The drug product of claim 17, wherein themedicament is beclomethasone dipropionate.
 27. The drug product of claim17, wherein the medicament is the combination of salmeterol xinafoateand fluticasone propionate.
 28. The drug product of claim 17, whereinthe medicament is salmeterol xinafoate and a salt, ester or solvate ofipratropium.
 29. The drug product of claim 17, wherein the aerosolcanister includes a ferrule; wherein the actuator includes a bodyhousing the actuation indicator; and, wherein the actuation indicatorincludes a tubular member adapted to receive the ferrule.
 30. The drugproduct of claim 17, wherein the actuator further includes a window toadapted to display numerals on one or more digit wheels engaging thestar wheel.
 31. The drug product of claim 30 comprising 3 digit wheelseach having numerals 0 through
 9. 32. A drug product comprising: a meansfor containing a drug formulation comprising a propellant and amedicament, a means for metering the drug formulation; a means foractuating the containing means; a means for removably engaging thecontaining and actuating means; a means for indicating actuations; and,a means for fixedly engaging the containing and indicating means.
 33. Adrug product for dispensing a drug formulation comprising a propellantand a medicament comprising: a means for containing the drugformulation; a means for supporting the containing means; a means forindicating actuation of the containing means; a means for fixedlyengaging the containing and indicating means; and, a means for housingthe containing, supporting, and indicating means.
 34. A method oftreating a patient comprising: providing the drug product of claim 17;actuating the drug formulation into the lungs of the patient; and,indexing the actuation indicator.
 35. The method of claim 34 furtherincluding the acts of: removing the container and actuation indicatorassembly from the housing; cleaning the housing; and, re-inserting theassembly into the cleaned housing.
 36. A method of treating a patientcomprising: providing the drug product of claim 1; actuating the drugformulation into the lungs of the patient; and, indexing the actuationindicator.
 37. The method of claim 36 further including the acts of:removing the aerosol canister and actuation indicator assembly from theactuator; cleaning the actuator; and, re-inserting the assembly into thecleaned actuator.